Mitigating dithiothreitol interference to gold/thiol interface in electrochemical detection of cathepsin B activity toward multiplex protease analysis.

Proteases are overexpressed at various stages of conditions such as cancers and thus can serve as biomarkers for disease diagnosis. Electrochemical techniques to detect the activity of extracellular proteases have gained attraction due to their multiplexing capability. Here we employ an electrochemical approach based on a 3 × 3 gold (Au) microelectrode array (MEA) functionalized with (2-aminoethyl)ferrocene (AEF) tagged specific peptide substrates to monitor cathepsin B (CB) protease activity.

Assessing consistency in drought risks in India with multiple multivariate meteorological drought indices (MMDI) under climate change.

This study investigates the spatio-temporal consistency of different MMDI formulations and their role in meteorological drought characterization uncertainty under historic and future climates using ERA5 reanalysis, and outputs from eight Coupled Model Intercomparison Project Phase 6 models, respectively, across different climate zones and shared socioeconomic pathways (SSP) in the Indian subcontinent. Six MMDI formulations namely the Standardized Precipitation Evaporation Index (SPEI), Reconnaissance Drought Index (RDI), and self-calibrated Palmer Drought Severity Index (scPDSI), Standardized Palmer Drought Index (SPDI), Standardized Moisture Anomaly Index (SZI) and Supply Demand Drought Index (SDDI) are used. A suite of analysis including agreement mapping, category difference analysis and uncertainty contribution analysis using global sensitivity analysis (GSA) are employed to quantify the consistency of MMDIs and uncertainty in drought characterization due to the MMDI formulation.

Development of a comprehensive food glycomic database and its application: Associations between dietary carbohydrates and insulin resistance.

Carbohydrates are an integral part of a healthy diet. The molecular compositions of carbohydrates encompass a very broad range of unique structures with many being ill-defined. This vast structural complexity is distilled into vague categories such as total carbohydrates, sugars, starches, and soluble/insoluble fibers.

Pylb-based overexpression of cytochrome P450 in Bacillus subtilis 168.

Inducer-free expression systems are promising tools for biorefinery because they can reduce the reliance on inducers, reducing production costs and simplifying processes. Owing to their broad range of substrate structures and catalytic reactions, cytochrome P450s are promising biocatalysts to produce value-added compounds. However, unsuitable levels of cytochrome P450 expression could result in cell stress, affecting the efficiency of the biocatalyst.

How likely is it that a virus or bacteria is causing a patient's symptoms? A new approach to interpret the outcome from multi-pathogen PCR.

Background: Whether a detected virus or bacteria is a pathogen that may require treatment, or is merely a commensal 'passenger', remains confusing for many infections. This confusion is likely to increase with the wider use of multi-pathogen PCR.

Objectives: To propose a new statistical procedure to analyse and present data from case-control studies clarifying the probability of causality.

The first reported case of candidemia caused by the novel Candida tropicalis diploid sequence type 1515.

Introduction: Since the dawn of the new millennium, Candida species have been increasingly implicated as a cause of both healthcare-associated as well as opportunistic yeast infections, due to the widespread use of indwelling medical devices, total parenteral nutrition, systemic corticosteroids, cytotoxic chemotherapy, and broad-spectrum antibiotics. Candida tropicalis is a pathogenic Candida species associated with considerable morbidity, mortality, and drug resistance issues on a global scale.

Methodology: We report a case of a 43-year-old man who was admitted to our hospital for further management of severe coronavirus disease 2019 (COVID-19) pneumonia.

Blood-based epigenome-wide association study and prediction of alcohol consumption.

Alcohol consumption is an important risk factor for multiple diseases. It is typically assessed via self-report, which is open to measurement error through recall bias. Instead, molecular data such as blood-based DNA methylation (DNAm) could be used to derive a more objective measure of alcohol consumption by incorporating information from cytosine-phosphate-guanine (CpG) sites known to be linked to the trait.

Optimization of metal polymer friction pair composition for hydrogen wear reduction through thermal stabilization analysis.

The composition of the metal-polymer friction pair is carefully considered for interacting with water and hydrogen, ensuring the metals electrode process potential remains below waters in a neutral medium. Simultaneously, adherence to defined chemical composition ratios for the metal-polymer materials is crucial. This analysis is conducted under conditions of thermal stabilization, characterized by a minimal temperature gradient across the rim thickness within an equivalent thermal field.

Exogenous dsRNA triggers sequence-specific RNAi and fungal stress responses to control Magnaporthe oryzae in Brachypodium distachyon.

In vertebrates and plants, dsRNA plays crucial roles as PAMP and as a mediator of RNAi. How higher fungi respond to dsRNA is not known. We demonstrate that Magnaporthe oryzae (Mo), a globally significant crop pathogen, internalizes dsRNA across a broad size range of 21 to about 3000 bp.

[Formula: see text]-roaming dynamics in the formation of [Formula: see text] following two-photon double ionization of ethanol and aminoethanol.

Roaming reactions involving a neutral fragment of a molecule that transiently wanders around another fragment before forming a new bond are intriguing and peculiar pathways for molecular rearrangement. Such reactions can occur for example upon double ionization of small organic molecules, and have recently sparked much scientific interest. We have studied the dynamics of the [Formula: see text]-roaming reaction leading to the formation of [Formula: see text] after two-photon double ionization of ethanol and 2-aminoethanol, using an XUV-UV pump-probe scheme.

Liquid-based encapsulation for implantable bioelectronics across broad pH environments.

Wearable and implantable bioelectronics that can interface for extended periods with highly mobile organs and tissues across a broad pH range would be useful for various applications in basic biomedical research and clinical medicine. The encapsulation of these systems, however, presents a major challenge, as such devices require superior barrier performance against water and ion penetration in challenging pH environments while also maintaining flexibility and stretchability to match the physical properties of the surrounding tissue. Current encapsulation materials are often limited to near-neutral pH conditions, restricting their application range.

Anthracyclines disaggregate and restore mutant p63 function: a potential therapeutic approach for AEC syndrome.

Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC) syndrome is a rare genetic disorder caused by mutations in the TP63 gene, which encodes a transcription factor essential for epidermal gene expression. A key feature of AEC syndrome is chronic skin erosion, for which no effective treatment currently exists. Our previous studies demonstrated that mutations associated with AEC syndrome lead to p63 protein misfolding and aggregation, exerting a dominant-negative effect.

Supramolecular discrimination and diagnosis-guided treatment of intracellular bacteria.

Pathogenic intracellular bacteria pose a significant threat to global public health due to the barriers presented by host cells hindering the timely detection of hidden bacteria and the effective delivery of therapeutic agents. To address these challenges, we propose a tandem diagnosis-guided treatment paradigm. A supramolecular sensor array is developed for simple, rapid, accurate, and high-throughput identification of intracellular bacteria.

Cerebral perfusion correlates with amyloid deposition in patients with mild cognitive impairment due to Alzheimer's disease.

Background: Changes in cerebral blood flow (CBF) may contribute to the initial stages of the pathophysiological process in patients with Alzheimer's disease (AD). Hypoperfusion has been observed in several brain regions in patients with mild cognitive impairment (MCI). However, the clinical significance of CBF changes in the early stages of AD is currently unclear.

Impella versus Non-Impella for Non-emergent High-Risk Percutaneous Coronary Intervention: Impella vs. Non-Impella for HR-PCI.

Background: The benefit of mechanical circulatory support (MCS) with Impella (Abiomed, Inc, Danvers, MA) for patients undergoing non-emergent, high-risk percutaneous coronary intervention (HR-PCI) is unclear and currently the subject of a large randomized clinical trial (RCT), PROTECT IV. While contemporary registry data from PROTECT III demonstrated improvement of outcomes with Impella when compared with historical data (PROTECT II), there is lack of direct comparison to the HR-PCI cohort that did not receive Impella support.

Methods: We retrospectively identified patients from our institution meeting PROTECT III inclusion criteria (left ventricular ejection fraction [LVEF] <35% with unprotected left main or last remaining vessel or LVEF <30% undergoing multivessel PCI), and compared this group (NonIMP) to the published outcomes data from the PROTECT III registry (IMP).

Advances in IgY antibody dosage form design and delivery strategies: Current status and future perspective.

Immunoglobulin Y (IgY), a unique type of antibody found in birds, is attracting increasing attention for a broad range of biomedical applications. Rational IgY protection, dosage form design, and delivery are highly essential to transform functional IgY antibodies into desired IgY products for therapeutic and prophylactic administration. Although progress has been made in this field, it remains in the early stages, highlighting the fundamental research and development needed in this aspect of IgY technology.

Self-assembled aptamer nanoparticles for enhanced recognition and anticancer therapy through a lysosome-independent pathway.

Aptamers and aptamer-drug conjugates (ApDCs) have shown some success as targeted therapies in cancer theranostics. However, their stability in complex media and their capacity to evade lysosomal breakdown still need improvement. To address these challenges, we herein developed a one-step self-assembly strategy to improve the stability of aptamers or ApDCs, while simultaneously enhancing their delivery performance and therapeutic efficiency through a lysosome-independent pathway.

Amyotrophic lateral sclerosis caused by FUS mutations: advances with broad implications.

Autosomal dominant mutations in the gene encoding the DNA and RNA binding protein FUS are a cause of amyotrophic lateral sclerosis (ALS), and about 0·3-0·9% of patients with ALS are FUS mutation carriers. FUS-mutation-associated ALS (FUS-ALS) is characterised by early onset and rapid progression, compared with other forms of ALS. However, different pathogenic mutations in FUS can result in markedly different age at symptom onset and rate of disease progression.

Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study.

Background: Given burdensome side-effects and long latency for efficacy with conventional agents, there is a continued need for generalised myasthenia gravis treatments that are safe and provide consistently sustained, long-term disease control. Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with generalised myasthenia gravis in a phase 2 study. We aimed to assess the safety and efficacy of nipocalimab in a phase 3 study.

Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection.

More than 50% of families with suspected rare monogenic diseases remain unsolved after whole-genome analysis by short-read sequencing (SRS). Long-read sequencing (LRS) could help bridge this diagnostic gap by capturing variants inaccessible to SRS, facilitating long-range mapping and phasing and providing haplotype-resolved methylation profiling. To evaluate LRS's additional diagnostic yield, we sequenced a rare-disease cohort of 98 samples from 41 families, using nanopore sequencing, achieving per sample ∼36× average coverage and 32-kb read N50 from a single flow cell.

Early childhood educators' perspectives of the social functioning and strengths of children exposed to intimate partner violence.

Background: Exposure to IPV can negatively impact children's social functioning. However, children exposed to IPV can also display significant strengths. The early educational environment can be a key factor promoting resilience outside of the family, with early educators in an ideal position to identify a broad range of social challenges, strengths and needs of children exposed to IPV.

Rewiring cancer: 3D genome determinants of cancer hallmarks.

In modern cancer biology, Hanahan and Weinberg's classic depiction of the Hallmarks of Cancer serves as a heuristic for understanding malignant phenotypes [1]. Genetic determinants of these phenotypes promote cancer induction and progression, and these mutations drive current approaches to understanding and treating cancer. Meanwhile, for over a century, pathologists have noted that profound alterations of nuclear structure accompany transformation, integrating these changes into diagnostic classifications (Figure 1).

The combination of hyperspectral imaging, untargeted metabolomics and lipidomics highlights a coordinated stress-related biochemical reprogramming triggered by polyethylene nanoparticles in lettuce.

Polyethylene nanoplastics (NPs) are widely diffused in terrestrial environments, including soil ecosystems, but the stress mechanisms in plants are not well understood. This study aimed to investigate the effects of two increasing concentrations of NPs (20 and 200 mg kg of soil) in lettuce. To this aim, high-throughput hyperspectral imaging was combined with metabolomics, covering both primary (using NMR) and secondary metabolism (using LC-HRMS), along with lipidomics profiling (using ion-mobility-LC-HRMS) and plant performance.

MetAssimulo 2.0: a web app for simulating realistic 1D & 2D Metabolomic 1H NMR spectra.

Unlabelled: Metabolomics extensively utilizes Nuclear Magnetic Resonance (NMR) spectroscopy due to its excellent reproducibility and high throughput. Both one-dimensional (1D) and two-dimensional (2D) NMR spectra provide crucial information for metabolite annotation and quantification, yet present complex overlapping patterns which may require sophisticated machine learning algorithms to decipher. Unfortunately, the limited availability of labeled spectra can hamper application of machine learning, especially deep learning algorithms which require large amounts of labelled data.

The activity of indigo carmine against bacteriophages: an edible antiphage agent.

Bacteriophage infections in bacterial cultures pose a significant challenge to industrial bioprocesses, necessitating the development of innovative antiphage solutions. This study explores the antiphage potential of indigo carmine (IC), a common FDA-approved food additive. IC demonstrated selective inactivation of DNA phages (P001, T4, T1, T7, λ) with the EC values ranging from 0.